Improvement of liver cell therapy in rats by dietary stearic acid

Background: Stearic acid is known as a potent anti-inflammatory lipid. This fatty acid has profound and diverse effects on liver metabolism. The aim of this study was to investigate the effect of stearic acid on markers of hepatocyte transplantation in rats with acetaminophen [APAP]-induced liver damage

Methods: Wistar rats were randomly assigned to 10-day treatment. Stearic acid was administered to the rats with APAP-induced liver damage. The isolated liver cells were infused intraperitoneally into rats. Blood samples were obtained to evaluate the changes in the serum liver enzymes, including activities of aspartate aminotransferase [AST], alanine aminotransferase [ALT] and alkaline phosphatase [ALP] and the level of serum albumin. To assess the engraftment of infused hepatocytes, rats were euthanized, and the liver DNA was used for PCR using sex-determining region Y [SRY] primers

Results: The levels of AST, ALT and ALP in the serum of rats with APAP-induced liver INJURY were significantly increased and returned to the levels in control group by day six. The APAP-induced decrease in albumin was significantly improved in rats through cell therapy, when compared with that in the APAP-alone treated rats. SRY PCR analysis showed the presence of the transplanted cells in the liver of transplanted rats

Conclusion: Stearic acid-rich diet in combination with cell therapy accelerates the recovering of hepatic dysfunction in a rat model of liver injury

Study of the antioxidant effects of Eremostachys laciniata rhizome extracts in isolated rat hepatocytes

Eremostachys laciniata, having rich flavonoids content, is expected to have a considerable antioxidant effects. We used ACMS [Accelerated cytotoxic or protective mechanism screening technique] to evaluate possible antioxidant effect of E. laciniata rhizome against oxidative cell damages induced by different types of oxidative stress such as iron-8-hydroxyquinolin [IQ] complex and copper in freshly isolated liver cells. The extracts were prepared with n-hexane, dichloromethane and methanol. Hepatocytes were isolated from male Sprague-Dawley rats by a two-step collagenase perfusion. Cell viability was measured by trypan blue exclusion method. DPPH [2, 2-diphenyl-1-picrylhydrazyl] assay was used to evaluate the antioxidant activity. ROS formation was measured by using DCFDA [2, 7-dichlorofluorescin diacetate] probe, mitochondrial membrane potential [MMP] was assessed by rhodamine 123 fluorescence and lipid peroxidation was determined by thiobarbituric acid reactive substances [TBARS] assay. The MET extract was demonstrated to possess a significant radical scavenging activity [RC50%=0.212]. Unlike MET extract, the n-hexane and dichloromethane extracts showed toxic effects in cell suspensions. The MET extract significantly decreased cell death and ROS formation induced by IQ complex and copper and demonstrated protective effects against copper-induced mitochondrial membrane potential collapse and lipid peroxidation. The protection induced by MET extract can be attributed to antioxidant characteristics of phenylethanoids content

Biological evaluation of a siliconized analog of clofibrate [silafibrate] in rodents

Silicon is the element very similar to carbon, and bioactive siliconized compounds have therefore received much attention. Siliconization of a compound enhances its biological activities. In the present study the hypolipidemic effect and toxicity of clofibrate and its siliconized analog, silafibrate, were compared. The experiments were performed in hypercholesterolemic Wistar rats. Animals received high fat diet with 62.75% normal chow, 2% cholesterol, 0.25% cholic acid, 15% lard oil, 10% wheat flour and 10% sucrose. Silafibrate[40 mg/kg/day] produced a predominant reduction in the serum levels of total cholesterol [28.4%, p < 0.001], triglycerides [62%, p < 0.0001] and low-density lipoproteins [27%, p < 0.001] being more effective than the reference drug clofibrate [20%, 40%, 14.5%; p < 0.05]. Similarly, it increased the total antioxidant levels in serum by 40% [p < 0.05]. Simultaneously, treatment with silafibrate also reduced the malondialdehyde [MDA] concentration by 41% [p < 0.05]. LD[50] of silafibrate, given orally, was greater than 2000 mg/kg body weight in albino mice while LD[50] for clofibrate was calculated to be 1220 mg/kg. Thirty-day subacute toxicity was also evaluated with oral daily dose at 25, 50 and 100 mg/kg body weight in Wistar rats. No significant changes in body weight, food intake, behavior, mortality, hematology, blood biochemistry, vital organ weight were detected. The results of this study indicate that the effectiveness and safety of the hypolipidemic drug, clofibrate, were enhanced remarkably by replacing chlorine atom in its phenoxy ring with trimethylsilyl

Synthesis of a novel siliconized analog of clofibrate [silafibrate] and comparison of their anti-inflammatory activities

Fibrates, as hypolipidemic drugs known as agonists of peroxisome proliferator-activated receptors, diminish inflammatory responses. Studies have shown that incorporation of a silicon atom into a drug structure improves its pharmacological potency, modifies its selectivity toward a given target, or changes its metabolic rate, in addition to increasing the lipophilicity of the compounds. A siliconized analog of clofibrate, ethyl-2-methyl-2-[4-[trimethylsilyl]phenoxy]propionate was synthesized, whereby the chlorine atom in the phenoxy ring was replaced by a trimethylsilyl group. The anti-inflammatory effects of the siliconized analog [silafibrate] were evaluated in an air-pouch model of inflammation and compared with those of clofibrate. Oral administration of both drugs produced a significant anti-inflammatory action by reducing carrageenan induced pouch leukocyte recruitment, exudates production, and granulated tissue weight. The silicon isostere of clofibrate has improved anti-inflammatory properties